Background: Little is known of the importance of social support in the associations between psychological distress and somatic health problems and socio-economic factors among older adults living at home. The objectives of the present study were to investigate the associations of social support, somatic health problems and socio-economic factors with psychological distress. We also examined changes in the association of somatic health problems and socio-economic factors with psychological distress after adjusting for social support. Methods: A random sample of 4,000 persons aged 65 years or more living at home in Oslo was drawn. Questionnaires were sent by post, and the total response was 2,387 (64%). Psychological distress was assessed using Hopkins Symptom Checklist (HSCL-10) and social support with the Oslo-3 Social Support Scale (OSS-3). A principal component analysis (PCA) included all items of social support and psychological distress. Partial correlations were used, while associations were studied by logistic regression. Results: After adjusting for socio-demographics and somatic health problems, we reported a statistically significant association between psychological distress and social support: “Number of close friends”, OR 0.61; 95% CI 0.47-0.80; “Concern and interest”, OR 0.68; 95% CI 0.55-0.84. A strong association between lack of social support and psychological distress, irrespective of variables adjusted for, indicated a direct effect. The associations between psychological distress and physical impairments were somewhat reduced when adjusted for social support, particularly for hearing, whereas the associations between somatic diagnoses and psychological distress were more or less eliminated. Income was found to be an independent determinant for psychological distress. Conclusions: Lack of social support and somatic health problems were associated with psychological distress in elders. Social support acted as a mediator, implying that the negative effect of somatic health problems, especially hearing, on psychological distress was mediated by low social support. We hypothesize that physical impairments reduced social support, thereby increasing psychological distress to a greater extent than the selected diagnoses. The combination of poor social support, poor somatic health and economic problems may represent a vulnerable situation with respect to the mental health of older persons. Free interventions that highlight social support should be considered in mental health promotion.